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接受放化疗的鼻咽癌患者唾液微生物群的变化

Changes of saliva microbiota in nasopharyngeal carcinoma patients under chemoradiation therapy.

作者信息

Xu Yuan, Teng Fei, Huang Shi, Lin Zhengmei, Yuan Xiao, Zeng Xiaowei, Yang Fang

机构信息

Department of Stomatology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.

Department of Operative Dentistry and Endodontics, Guanghua School and Hospital of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China.

出版信息

Arch Oral Biol. 2014 Feb;59(2):176-86. doi: 10.1016/j.archoralbio.2013.10.011. Epub 2013 Nov 4.

Abstract

OBJECTIVE

A growing body of evidence has implicated human oral microbiota in the aetiology of oral and systemic diseases. Nasopharyngeal carcinoma (NPC), an epithelial-originated malignancy, has a complex aetiology not yet fully understood. Chemoradiation therapy of NPC can affect oral microbiota and is usually accompanied by plaque accumulation. Thus, the study aimed to understand the diversity, divergence and development of the oral microbiota in NPC patients and their associated treatment, which might provide useful insights into disease aetiology and treatment side effects.

DESIGN

A longitudinal study was designed that included three Chinese adults with NPC. Saliva samples were collected at three time points: prior to the chemoradiation treatment (carcinoma baseline, or CB), 7 months post-treatment (carcinoma-after-therapy phase 1 or CA1) and 12 months post-treatment (carcinoma-after-therapy phase 2 or CA2). Pyrosequencing of the bacterial 16S ribosomal DNA (rDNA) V1-V3 hypervariable region was employed to characterise the microbiota. Saliva samples of three healthy subjects from our former study were employed as healthy controls. Principal coordinates analysis (PCoA), Metastats and random forest prediction models were used to reveal the key microbial members associated with NPC and its treatment programme.

RESULTS

(1) In total, 412 bacterial species from at least 107 genera and 13 phyla were found in the saliva samples of the NPC patients. (2) PCoA revealed that not only were the microbiota from NPC patients distinct from those of healthy controls (p<0.001) but also that separation was found on the saliva microbiota between pre- and post-therapy (p<0.001) in the NPC samples. (3) At the genus level and the operational taxonomic unit (OTU) level, Streptococcus was found with lower abundance in NPC samples. (4) Chemoradiation therapy did not incur similar changes in microbiota structure among the three NPC patients; the microbiota in one of them stayed largely steady, while those in the other two showed significant alteration.

CONCLUSIONS

This is the first study employing culture-independent techniques to interrogate the phylogenetic diversity, divergence and temporal development of oral microbiota in NPC patients. Our results indicated that certain bacterial taxa might be associated with NPC and that oral microbiota of NPC patients might respond to the chemoradiation therapy in a host-specific manner. Further investigation with larger sample size should help to validate the links between oral microbiota and NPC.

摘要

目的

越来越多的证据表明,人类口腔微生物群与口腔及全身疾病的病因有关。鼻咽癌(NPC)是一种上皮源性恶性肿瘤,其病因复杂,尚未完全明确。NPC的放化疗会影响口腔微生物群,且通常伴有菌斑积聚。因此,本研究旨在了解NPC患者口腔微生物群的多样性、差异及发展情况,以及其相关治疗,这可能为疾病病因及治疗副作用提供有用的见解。

设计

设计了一项纵向研究,纳入了三名成年中国NPC患者。在三个时间点采集唾液样本:放化疗前(癌基线,或CB)、治疗后7个月(治疗后癌阶段1或CA1)和治疗后12个月(治疗后癌阶段2或CA2)。采用细菌16S核糖体DNA(rDNA)V1-V3高变区焦磷酸测序来表征微生物群。将我们之前研究中的三名健康受试者的唾液样本用作健康对照。主坐标分析(PCoA)、Metastats和随机森林预测模型用于揭示与NPC及其治疗方案相关的关键微生物成员。

结果

(1)在NPC患者的唾液样本中,共发现了至少107个属和13个门的412种细菌。(2)PCoA显示,不仅NPC患者的微生物群与健康对照不同(p<0.001),而且在NPC样本中,治疗前后的唾液微生物群也存在差异(p<0.001)。(3)在属水平和操作分类单元(OTU)水平上,发现NPC样本中链球菌的丰度较低。(4)放化疗在三名NPC患者中并未引起微生物群结构的类似变化;其中一名患者的微生物群基本保持稳定,而另外两名患者的微生物群则出现了显著改变。

结论

这是第一项采用非培养技术研究NPC患者口腔微生物群的系统发育多样性、差异及时间发展的研究。我们的结果表明,某些细菌类群可能与NPC有关,且NPC患者的口腔微生物群可能以宿主特异性方式对放化疗产生反应。更大样本量进一步研究应有助于验证口腔微生物群与NPC之间的联系。

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